Mesenchymal stromal cells from JAK2.sup.+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis

There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expressi...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2017-08, Vol.12 (8), p.e0182470
Main Authors: Ramos, Teresa L, Sánchez-Abarca, Luis Ignacio, Rosón-Burgo, Beatriz, Redondo, Alba, Rico, Ana, Preciado, Silvia, Ortega, Rebeca, Rodríguez, Concepción, Muntión, Sandra, Hernández-Hernández, Ángel, De Las Rivas, Javier, González, Marcos, González Porras, José Ramón, del Cañizo, Consuelo, Sánchez-Guijo, Fermín
Format: Article
Language:English
Subjects:
Care and treatment
Diagnosis
Fluorescence
Gene expression
Hematopoiesis
Myeloproliferative disorders
Stem cells
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HD-MSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls. Gene expression profile of BM-MSC showed a total of 169 genes that were differentially expressed in BM-MSC from MPN patients compared to HD-MSC. In addition, we studied the ability of BM-MSC to support the growth and survival of hematopoietic stem/progenitor cells (HSPC), showing a significant increase in the number of CFU-GM colonies when MPN-HSPC were co-cultured with MPN-MSC. Furthermore, MPN-MSC showed alteration in the expression of genes associated to the maintenance of hematopoiesis, with an overexpression of SPP1 and NF-kB, and a downregulation of ANGPT1 and THPO. Our results suggest that BM-MSC from JAK2.sup.+ patients differ from their normal counterparts and favor the maintenance of malignant clonal hematopoietic cells.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0182470